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  • Abstract: Veins x
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Satoshi Higuchi Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Hideki Ota Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Advanced MRI Collaboration Research, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Yuta Tezuka Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Kazumasa Seiji Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Hidenobu Takagi Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Jongmin Lee Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Korea

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Yi-Wei Lee Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Kei Omata Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Yoshikiyo Ono Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Ryo Morimoto Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

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Masataka Kudo Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

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Fumitoshi Satoh Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Kei Takase Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Objectives

This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.

Design

A retrospective, single-center, observational study.

Methods

We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images.

Results

PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047).

Conclusions

APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.

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H A Booij Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands

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W D C Gaykema Roessingh Rehabilitation Center, Enschede, the Netherlands

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K A J Kuijpers Roessingh Rehabilitation Center, Enschede, the Netherlands

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M J M Pouwels Department of Endocrinology, Medisch Spectrum Twente, Enschede, the Netherlands

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H M den Hertog Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands

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Background

Poststroke fatigue (PSF) is a highly prevalent and debilitating condition. However, the etiology remains incompletely understood. Literature suggests the co-prevalence of pituitary dysfunction (PD) with stroke, and the question raises whether this could be a contributing factor to the development of PSF. This study reviews the prevalence of PD after stroke and other acquired brain injuries and its association with fatigue.

Summary

We performed a bibliographic literature search of MEDLINE and EMBASE databases for English language studies on PD in adult patients with stroke, traumatic brain injury (TBI) or aneurysmatic subarachnoid hemorrhage (aSAH). Forty-two articles were selected for review. Up to 82% of patients were found to have any degree of PD after stroke. Growth hormone deficiency was most commonly found. In aSAH and TBI, prevalences up to 49.3% were reported. However, data differed widely between studies, mostly due to methodological differences including the diagnostic methods used to define PD and the focus on the acute or chronic phase. Data on PD and outcome after stroke, aSAH and TBI are conflicting. No studies were found investigating the association between PD and PSF. Data on the association between PD and fatigue after aSAH and TBI were scarce and conflicting, and fatigue is rarely been investigated as a primary end point.

Key messages

Data according to the prevalence of PD after stroke and other acquired brain injury suggest a high prevalence of PD after these conditions. However, the clinical relevance and especially the association with fatigue need to be established.

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Ashley N Reeb Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Andrea Ziegler Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Reigh-Yi Lin Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

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Richard W Carroll Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand

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Brian Corley Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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Joe Feltham Department of Radiology, Wellington Regional Hospital, New Zealand

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Patricia Whitfield Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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William Park University of Otago, Wellington, New Zealand

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Rowena Howard Diabetes and Endocrinology Service, Hutt Hospital, New Zealand

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Melissa Yssel Department of Biochemistry & Endocrinology, Awanui Labs, New Zealand

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Ian Phillips Department of Biochemistry, Awanui Labs, Dunedin, New Zealand

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Simon Harper Department of Surgery & Anaesethesia, University of Otago, Wellington, New Zealand
Department of General Surgery, Wellington Regional Hospital, New Zealand

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Jun Yang Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Medicine, Monash University, Clayton, Victoria, Australia

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Objective

The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS.

Design

This is a diagnostic accuracy study in a tertiary referral endocrinology department.

Methods

Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS.

Results

There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet–PVmet) of ≥12.0 to indicate successful cannulation of the AV (n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet–AVnormet) of ≥2.0 to indicate successful cannulation (n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization (n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%).

Conclusions

Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy.

Significance statement

Primary aldosteronism is a common cause of secondary hypertension, and adrenal vein sampling remains the gold standard test to assess lateralization. Cortisol-derived ratios to assess cannulation and lateralization may be affected by concurrent cortisol dysfunction, which is not uncommon in the context of primary aldosteronism. Our study showed comparable outcomes when using accepted cortisol-derived or metanephrine-derived ratios to determine cannulation and lateralization during adrenal vein sampling. Further research is required to validate these findings and to assess the use of metanephrine-derived ratios in the context of confirmed concurrent cortisol dysfunction.

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Ermina Bach Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Niels Møller Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jens Otto L Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Mads Buhl The Neonatal Intensive Care Unit, Aarhus University Hospital, Aarhus, Denmark

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Holger Jon Møller Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

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Aims/hypothesis

The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner.

Methods

We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively.

Results:

Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163.

Conclusion:

Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.

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Eng-Loon Tng Department of Medicine, Level 8, Tower A, Ng Teng Fong General Hospital, Singapore

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Yee Sian Tiong Department of Medicine, Level 8, Tower A, Ng Teng Fong General Hospital, Singapore

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Aye Thida Aung Department of Medicine, Level 8, Tower A, Ng Teng Fong General Hospital, Singapore

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Nicole Ya Yuan Chong Department of Medicine, National University Hospital, Singapore

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Zhemin Wang Department of Medicine, National University Hospital, Singapore

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Background

Evidence on the efficacy and safety of anticoagulation in preventing stroke and thromboembolic events in people with thyrotoxic atrial fibrillation is scarce.

Objective

We evaluated the efficacy and safety of anticoagulation in people with thyrotoxic atrial fibrillation.

Methods

Our study protocol was published in the International Prospective Register of Systematic Reviews (registration no. CRD42020222782). Four databases and two systematic review registers were searched through 25 November 2020 for interventional and observational studies comparing anticoagulation therapy with active comparators, placebo, or no treatment in people with thyrotoxic atrial fibrillation. Random-effects meta-analysis and sensitivity analysis were performed. Quality of evidence was described using the GRADE framework.

Results

In the study, 23,145 records were retrieved. One randomized controlled trial and eight cohort studies were ultimately included. Effect estimates on the efficacy and safety of anticoagulation were extracted. Meta-analysis using the inverse variance and random-effects methods was conducted on four cohort studies with 3443 participants and 277 events. Anticoagulation in people with thyrotoxic atrial fibrillation reduced the risk of ischemic stroke and systemic thromboembolism by 3% (95% CI: 1–6%). Warfarin may prevent ischemic stroke in people with thyrotoxic atrial fibrillation if the CHA2DS2-VASc score exceeds 1 and when atrial fibrillation persists beyond 7 days. Direct oral anticoagulants may be associated with fewer bleeding events than warfarin.

Conclusions

Anticoagulation prevents ischemic stroke and systemic thromboembolism in people with thyrotoxic atrial fibrillation. Direct oral anticoagulants may be associated with fewer bleeding events.

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Chaiho Jeong Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Bongseong Kim Department of Medical Statistics, Soongsil University of Korea, Seoul, Republic of Korea

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Jinyoung Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Hansang Baek Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Mee Kyoung Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Tae-Seo Sohn Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Ki-Hyun Baek Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Ki-Ho Song Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Hyun-Shik Son Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Kyungdo Han Department of Medical Statistics, Soongsil University of Korea, Seoul, Republic of Korea

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Hyuk-Sang Kwon Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Objective

Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce.

Methods

From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level: <55 mg/dL, 55–69 mg/dL, 70–99 mg/dL, 100–129 mg/dL, 130–159 mg/dL, and ≥ 160 mg/dL.

Results

Compared to LDL-C < 55 mg/dL, the hazard ratios (HR) for re-PCI and stroke increased linearly with increasing LDL-C level in the population < 65 years. However, in ≥ 65 years old, HRs for re-PCI and stroke in LDL-C = 55–69 mg/dL were 0.97 (95% CI: 0.85–1.11) and 0.96 (95% CI: 0.79–2.23), respectively. The optimal range with the lowest HR for heart failure and all-cause mortality were LDL-C = 70–99 mg/dL and LDL-C = 55–69 mg/dL, respectively, in all age groups (HR: 0.99, 95% CI: 0.91–1.08 and HR: 0.91, 95% CI: 0.81–1.01).

Conclusion

LDL-C level below 55 mg/dL appears to be optimal in T2DM patients with established cardiovascular disease aged < 65 years, while an LDL-C level of 55–69 mg/dL may be optimal for preventing recurrent PCI and stroke in patients over 65 years old.

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Sahar Hossam El Hini Diabetes and Endocrinology Unit, Department of Internal Medicine, Faculty of Medicine, Minia University, Minia, Egypt

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Yehia Zakaria Mahmoud Department of Internal Medicine, Faculty of Medicine, Minia University, Minia, Egypt

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Ahmed Abdelfadel Saedii Department of Clinical Pathology, Faculty of Medicine, Minia University, Minia, Egypt

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Sayed Shehata Mahmoud Department of Cardiology, Faculty of Medicine, Minia University, Minia, Egypt

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Mohamed Ahmed Amin Department of Radiology, Faculty of Medicine, Minia University, Minia, Egypt

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Shereen Riad Mahmoud Diabetes and Endocrinology Unit, Department of Internal Medicine, Faculty of Medicine, Minia University, Minia, Egypt

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Ragaa Abdelshaheed Matta Diabetes and Endocrinology Unit, Department of Internal Medicine, Faculty of Medicine, Minia University, Minia, Egypt

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Objective

Angiopoietin-like proteins (ANGPTL) 3, 4 and 8 are upcoming cardiovascular biomarkers. Experimental studies showed that thyroid hormones altered their levels. We assessed ANGPTL3, 4 and 8 as predictors of cardiovascular functions among naïve subclinical and naïve overt hypothyroidism (SCH and OH) and altered ANGPTL levels with levothyroxine replacement (LT4) and their association with improved cardiovascular risk factors and cardiovascular function.

Design and methods

The study was a prospective follow-up study that assessed ANGPTL3, 4 and 8 levels, vascular status (flow-mediated dilation% of brachial artery (FMD%), carotid intima-media thickness (CIMT), aortic stiffness index (ASI)), left ventricle (LV) parameters (ejection fraction (EF), myocardial performance index (MPI), and LV mass), well-known cardiovascular risk factors and homeostatic model for the assessment of insulin resistance, at two time points, that is, among naïve SCH, naïve OH, and healthy subjects groups; and at 6 months after achieving the euthyroid state with LT4 by calculating their increased or decreased delta changes (∆↑ or ∆↓) in longitudinal arm among LT4-hypothyroid groups.

Results

Significantly elevated levels of ANGPTL3, 4 and 8 among hypothyroid groups than the healthy subjects were reduced with LT4. Multivariate analysis revealed ANGPTLs as independent predictors of cardiovascular functions and the contributors for ANGPTL level included ANGPTL3 and 4 for impaired FMD%, and ANGPTL8 for LV mass among naïve SCH; ANGPTL3 for EF% and ANGPTL8 for CIMT in naïve OH; ∆↓ANGPTL3 for ∆↓ASI meanwhile ∆↑freeT4 for ∆↓ANGPTL3, ∆↓fasting glucose, ∆↓triglyceride, and ∆↓thyroid peroxidase antibody for ∆↓ANGPTL4 among LT4-SCH. ∆↓ANGPTL4 for ∆↓MPI and ∆↓LV mass, meanwhile ∆↓TSH and ∆↓triglyceride for ∆↓ANGPTL3, ∆↑free T3 and ∆↓HOMA-IR for ∆↓ANGPTL4, and systolic blood pressure and waist circumference for ∆↓ANGPTL8 among LT4-OH.

Conclusion

Elevated ANGPTL3, 4 and 8 levels are differentially independent predictors of endothelial and cardiac function and are reduced with LT4 in SCH and OH.

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Caishun Zhang Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Junhua Yuan Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Qian Lin Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Manwen Li Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Liuxin Wang Hyperbaric Oxygen Therapy Department, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China

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Rui Wang Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Xi Chen Physiology Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Zhengyao Jiang Physiology Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Kun Zhu Intensive Care Unit Department, Affiliated Hospital of Qingdao University, Qingdao, China

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Xiaoli Chang Institute of Acupuncture, Shandong University of Traditional Chinese Medicine, Jinan, China

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Bin Wang Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China
Medical Microbiology Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Jing Dong Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China
Physiology Department, College of Basic Medicine, Qingdao University, Qingdao, China

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Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR−/− mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR−/− mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

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Robert A Hart Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Robin C Dobos NSW Department of Primary Industries, Armidale, New South Wales, Australia

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Linda L Agnew Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Neil A Smart Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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James R McFarlane Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Pharmacokinetics of leptin in mammals has not been studied in detail and only one study has examined more than one time point in non-mutant mice and this was in a female mice. This is the first study to describe leptin distribution over a detailed time course in normal male mice. A physiologic dose (12 ng) of radiolabelled leptin was injected into adult male mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course of up to two hours. Major targets were the digestive tract, kidneys, skin and lungs. The brain was not a major target, and 0.15% of the total dose was recovered from the brain 5 min after administration. Major differences appear to exist in the distribution of leptin between the male and female mice, indicating a high degree of sexual dimorphism. Although the half-lives were similar between male and female mice, almost twice the proportion of leptin was recovered from the digestive tract of male mice in comparison to that reported previously for females. This would seem to indicate a major difference in leptin distribution and possibly function between males and females.

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